Bone-on-a-Chip: A Microscale 3D Biomimetic Model to Study Bone Regeneration

Organ-on-chip models, developed using microengineering and microfluidic technologies, aim to recreate physiological-like microenvironments of organs or tissues as a tool to study (patho)physiological processes in vitro. On-chip models of bone are relevant for the study of bone physiology, diseases and regenerative processes. While a few bone-on-a-chip models exist, recapitulating the cellular components of bone, these models do not incorporate the chemical and structural characteristics of bone tissue. Herein, the development of a bone-on-a-chip platform is reported that comprises a 3D structural model of bone. To build the platform, first, a 3D model of bone is produced in a polymer using two-photon polymerization (2PP) from a 3D nano-computed tomography scan of trabecular bone. This 3D model is then coated with a layer of bone mineral-like calcium phosphate. Finally, the 3D bone model is integrated inside a microfluidic device suitable for cell culture. Human mesenchymal stromal cells, cultured inside the platform for up to 21 days, show high viability and extensive production of extracellular matrix, rich in collagen. This biomimetic bone-on-a-chip platform can contribute to a better understanding of the processes related to bone formation and remodeling, which in turn can be used for the development of bone regeneration strategies.